A Dose-Finding Study of the Second Mitochondrial Activator of Caspases (SMAC) Mimetic Debio 1143 When Given in Combination With Avelumab to Participants With Advanced Solid Malignancies and to Participants With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC) After Platinum-Based Therapy

Debiopharm

Status and phase: Completed; Phase 1

Conditions: Neoplasms; Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Avelumab; Drug: Debio 1143

Study type: Interventional

Funder types: Industry

Identifiers

NCT03270176

Debio 1143-NSCLC-105

2018-000494-71 (EudraCT Number)

Details and patient eligibility

About

The study is primarily designed to assess the safety and tolerability of escalating oral doses of Debio 1143 and preliminary anti-tumour activity when combined with the standard dose of avelumab in participants with advanced solid malignancies.

Enrollment: 54 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Part A • With advanced solid malignancies who are not eligible for standard therapy or for whom standard therapy has failed

Part B

• With histologically or cytologically confirmed NSCLC of stage IIIB or IV (per 7th International Association for the Study of Lung Cancer classification) that has progressed after one line of platinum containing doublet chemotherapy

Part A and B

• Willingness and feasibility to provide a tumor biopsy sample both at screening and during treatment (If archived tumor material not older than 1 year is available, then the screening biopsy will not be performed).
• Participants with prior radiation therapy must have measurable disease in non-irradiated sites or documented evidence of progression within the radiation field.
• With known central nervous system (CNS) must have completed primary brain therapy (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection) and must have remained clinically stable, asymptomatic, and without steroid treatment for at least 21 days.

Exclusion criteria

• Not recovered (i.e. toxicity grade >1) from prior investigational drug and/or anti-cancer therapy (chemo- or palliative radiotherapy).
• Symptomatic and/or progressive brain metastasis or carcinomatous meningitis.
• Immunosuppressive agents (such as steroids) for any reason should be tapered off before initiation of study treatment (except low-dose prednisone at a total dose of up to 10 mg/day).

Part B only

• Tumor activating epidermal growth factor receptor (EGFR) mutation(s) or anaplastic lymphoma kinase (ALK)/ROS1 translocation/rearrangement (testing required in non-squamous participants if status is unknown).
• More than one prior line of chemotherapy and one line of anti-PD1/PDL1 therapy.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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54 participants in 1 patient group

Debio 1143 and Avelumab

Experimental group

Description:

Part A: Participants will receive Debio 1143 100 to 250 milligram (mg) capsule orally at an escalating dose levels for 10 days every 2 weeks along with avelumab 10 milligrams per kilogram (mg/kg) as an intravenous (IV) infusion every 2 weeks. Part B: Participants will receive Debio 1143 capsules orally at a recommended phase 2 dose (RP2D) of 200 mg/day (days 1-10 and 15-24 every 28 days (\[q4w\]) in combination with avelumab IV infusion at the standard dose unless disease progression or unacceptable toxicity occurs, as judged by investigators up to 26 cycles (each cycle is of 28 days).

Treatment:

Drug: Avelumab

Drug: Debio 1143